title: Different residues in channel turret determining the selectivity of ADWX-1 inhibitor peptide between Kv1.1 and Kv1.3 channels.
abstract: The low selectivity of Kv1 peptide inhibitors for specific isoforms makes them poor candidates for the development of theraputics. Using combined approaches, we showed that the Kv1 turret is the critical determinant for ADWX-1 peptide inhibitor selectivity of Kv1.3 over Kv1.1. Mutation of Kv1.1 turret residues to match the sequence of Kv1.3 lead to increased inhibition of Kv1.1 activity. These studies may lead to improvements in peptide inhibitor drug development.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Shi-Jin
authors.initials: SJ
authors.lastname: Yin
authors.forename: Ling
authors.initials: L
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Dai-Wen
authors.initials: DW
authors.lastname: Yang
authors.forename: Mai-Li
authors.initials: ML
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Cao
authors.forename: Ying-Liang
authors.initials: YL
authors.lastname: Wu
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D003198:Computer Simulation; D004220:Disulfides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006860:Hydrogen Bonding; D051662:Kv1.1 Potassium Channel / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid
chemical_list: D000596:Amino Acids; D004220:Disulfides; D051664:Kv1.3 Potassium Channel; D009842:Oligopeptides; D026902:Potassium Channel Blockers; D051662:Kv1.1 Potassium Channel